Sox2 与 Atoh1 和 Huwe1 Loci 相互作用,在毛细胞分化过程中调节 Atoh1 的转录和稳定性。

IF 4 2区 生物学 Q1 GENETICS & HEREDITY
PLoS Genetics Pub Date : 2025-01-30 eCollection Date: 2025-01-01 DOI:10.1371/journal.pgen.1011573
Yen-Fu Cheng, Judith S Kempfle, Hao Chiang, Kohsuke Tani, Quan Wang, Sheng-Hong Chen, Danielle Lenz, Wei-Yi Chen, Wenjin Wu, Marco Petrillo, Albert S B Edge
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引用次数: 0

摘要

干细胞多能性基因Sox2刺激原基螺旋环螺旋转录因子Atoh1的表达。Sox2是耳蜗毛细胞发育所必需的,并结合Atoh1 3'增强子刺激Atoh1的表达。我们在这里表明,在胚胎发生晚期,Sox2基因缺失导致了额外毛细胞的形成,而在妊娠早期,Sox2基因敲除后毛细胞发育缺失。Sox2过表达降低了Atoh1蛋白水平,尽管Atoh1 mRNA水平升高。Sox2通过直接结合Huwe1基因上调E3泛素连接酶Huwe1。通过上调其同源的E3连接酶,Sox2破坏了Atoh1蛋白增加Atoh1表达的正反馈环。我们得出结论,Sox2启动表达,同时也限制bHLH转录因子Atoh1的持续活性,这种抑制代表了调节这种强大的毛细胞发育启动器活性的新机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sox2 interacts with Atoh1 and Huwe1 loci to regulate Atoh1 transcription and stability during hair cell differentiation.

Stem cell pluripotency gene Sox2 stimulates expression of proneural basic-helix-loop-helix transcription factor Atoh1. Sox2 is necessary for the development of cochlear hair cells and binds to the Atoh1 3' enhancer to stimulate Atoh1 expression. We show here that Sox2 deletion in late embryogenesis results in the formation of extra hair cells, in contrast to the absence of hair cell development obtained after Sox2 knockout early in gestation. Sox2 overexpression decreased the level of Atoh1 protein despite an increase in Atoh1 mRNA. Sox2 upregulated E3 ubiquitin ligase, Huwe1, by direct binding to the Huwe1 gene. By upregulating its cognate E3 ligase, Sox2 disrupts the positive feedback loop through which Atoh1 protein increases the expression of Atoh1. We conclude that Sox2 initiates expression, while also limiting continued activity of bHLH transcription factor, Atoh1, and this inhibition represents a new mechanism for regulating the activity of this powerful initiator of hair cell development.

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来源期刊
PLoS Genetics
PLoS Genetics GENETICS & HEREDITY-
自引率
2.20%
发文量
438
期刊介绍: PLOS Genetics is run by an international Editorial Board, headed by the Editors-in-Chief, Greg Barsh (HudsonAlpha Institute of Biotechnology, and Stanford University School of Medicine) and Greg Copenhaver (The University of North Carolina at Chapel Hill). Articles published in PLOS Genetics are archived in PubMed Central and cited in PubMed.
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